Method for preparing fatty esters



2,997,490 METHOD FOR PREPARING FATTY ESTERS Wilson F. Huber, State College, Pa., assignor to The Procter & Gamble Company, Cincinnati, Ohio, a corporation of Ohio No Drawing. Filed May 8, I959, Ser. No. 811,786 5 Claims. (Cl. 26(l-'410) This invention relates to a process for preparing partial fatty esters of polyhydroxy-substituted cyclohexanes.

More specifically, this invention relates to the preparation of partial fatty esters of inositol.

The preparation of fatty esters of inositol utilizing a reaction between inositol and a free fatty acid or a fatty acid chloride are known. However, all such prior methods resulted in the formation of the complete fatty ester of inositol, i.e. the hexa-substituted inositol, regardless of the ratio of inositol to acylating agent in the reaction mixture. The complete fatty esters of inositol are not suitable for all purposes in which it is desired to employ an inositol derivative. Consequently, a method has long been sought whereby a partial fatty ester of inositol could be prepared readily and economically.

Prior to the invention disclosed and claimed herein the present inventor found that the only method by which partial esters of inositol could be prepared involved the use of liquid hydrogen fluoride as a solvent medium for reactants. However, even with this solvent, the acylating agent most usually had to be the free fatty acid or the acid chloride. Moreover, the use of liquid hydrogen fluoride as a solvent medium for the reaction was extremely hazardous and involved the use of special equip ment because of the extreme corrosiveness of the hydrogen fluoride.

With the foregoing considerations in mind, it is an object of this invention to provide a method whereby partial fatty esters of inositol can be prepared.

A further object of this invention is to provide a method whereby partial esters of inositol can be prepared readily and economically and under conditions which are not hazardous.

A still further object of this invention is to provide a method whereby partial fatty esters of inositol can be prepared with the exercise of control over the degree of esterification.

Other objects and advantages will be apparent from the following detailed description.

It has been found that the foregoing objects can be accomplished by subjecting to interesterification a mixture of inositol and a fatty acid ester of an aliphatic primary monohydroxy alcohol or a fatty acid ester of certain polyhydroxy alcohols in the presence of dimethyl sulfoxide.

Generally speaking, the invention contemplates reacting inositol with the fatty acid ester in the presence of an alkaline catalyst which shows activity in interesterification reactions, and in the presence of dimethyl sulfoxide. Following completion of the interesterification of the components to the desired degree, the catalyst is inactivated by the addition of water and/or acids such as acetic, phosphoric, citric, hydrochloric and the like, and the desired reaction products are freed from solvent and purified by any suitable means.

The fatty esters which can be employed in the reaction herein concerned are the. fatty acid esters of primary aliphatic monohydroxy alcohols having from 1 to 8 carbon atoms, for example, methanol, ethanol, hexanol and octanol, specific examples being methyl palmitate, ethyl palmitate and octyl palmitate. In addition, completely or incompletely esterified fatty acid esters of polyhydric alcohols having not more than three carbon atoms, such as ethylene glycol and glycerol can be employed. Of this States Patent 0 ice latter group of esters the fatty triglycerides have been found to be particularly advantageous reactants.

The length of the fatty acid chain of the esters which can be employed in the reaction of this invention is not critical and is dictated primarily by the type of fatty acid source material available. As a general proposition, however, it has been found that fatty acids containing from about 8 to 22 carbon atoms in the alkyl chain are most useful. Therefore, the mixtures of fatty acids obtained from animal, vegetable or marine oils and fats such as coconut oil, cottonseed oil, soybean oil, tallow, lard, herring oil, sardine oil, and the like, represent readily available sources of fatty acid radicals. In the event it is desired to produce inositol esters of single fatty acids by this invention, then the fatty acid esters of relatively volatile alcohols (e.g. methanol and ethanol), the fatty acid portions of which contain from about 12 to 22 carbon atoms, can be advantageously reacted with inositol utilizing the particular solvent herein disclosed as the reaction medium.

The choice of solvent is essential to the realization of interesterification of the inositol and the fatty esters under the conditions set forth herein. It has been found that dimethylsulfoxide is eminently suitable as the solvent reaction medium in the present process. This compound promotes a relatively rapid rate of reaction with minimum catalyst requirements and is not subject to decomposition during the interesterification reaction.

It is theorized that prior art methods resulted in the formation of only the hexa-substituted inositol because of the insolubility of inositol in the usual solvents. Therefore, as soon. as any portion of the inositol was esterified, the partially esterified product became more soluble in the solvent than the unreacted inositol, dissolved therein, and thereupon being in solution, reacted preferentially with the acylating agent to yield the hexa-acylated (complete) ester. In the present process, inositol is relatively soluble in dimethylsulfoxide and, as a result, there is no preferential acylation to the hexa-acylated form exclusively.

In general, the amount of dimethylsulfoxide solvent required for any given interesterification is not critical. Quantities of dimethylsulfoxide in amounts from about /6 to about 30 times the weight of the fatty ester employed for reaction with the inositol can be readily used.

. In any event, an amount of dimethylsulfoxide which is adequate to dissolve the inositol which is to be esterified should be employed. The solvent usage is normally adjusted depending upon the particular reactants which are to be interesterified and sufiicient solvent should be used so that the advantages associated with solvent usage, e.g. rapid interesterification, can be realized.

The proportions of reactants is not critical and is dietated primarily by the ultimate product which is desired. Thus, the proportions of the reactants, i.e. inositol and fatty ester, can be chosen so that any one or more of the hydrogen atoms of the hydroxyl groups of the inositol can be replaced by a fatty acyl radical. In general, the molecular proportions of the reactants will determine the degree of esterification of inositol. For example, if one mole of inositol and one mole of fatty ester is reacted, the product will be predominantly the inositol mono-fatty acid ester. If two moles of fatty ester are present for every one mole of inositol in the reaction medium the resultant product will be predominantly the di-fatty ester of inositol. Likewise, with a ratio of fatty ester of inositol Ii can be subjected to appropriate crystallization or solvent partition procedures to separate the desired fraction of the product.

Although the process of the invention is illustrated herein principally with the use of sodium methoxide as the catalyst, effective practice of the process is not dependent upon the use of any particular catalyst. Rather, any alkaline molecular rearrangement or interesterification catalyst which will promote the interchange of radicals among the reactants of the process is suitable. Examples of usable catalysts are sodium methoxide, sodium hydroxide, metallic sodium, sodium potassium alloy and quaternary ammonium bases such as trimethyl benzyl ammonium hydroxide. A discussion of other catalysts which are active in interesterification reactions may be found in U.S. Letters Patent 2,442,532 to E. W. Eckey, column 24, line 18 et seq.

Sodium methoxide catalyst can be advantageously used in the present invention in amounts from about 0.1% to about 2.0% by weight of the fatty ester which is to be reacted with the inositol. The choice of catalyst and the amount which is to be used are dependent upon the particular constituents which are to be reacted.

In the practice of the invention it was observed that the reaction rate for a given solvent usage and a given catalyst increased with an increase in temperature. Under substantially optimum conditions, and utilizing sodium methoxide as the catalyst, equilibrium can be reached in the interesterification reaction in from about 3 to 10 minutes time at a temperature of 100 C. Where lower temperatures, such as about 5 0 C. are to be employed, a longer time is necessary to achieve the desired ester formation. Temperatures above 100 C. and up to about 150 C. may be employed if desired. Generally speaking, with any of the aforementioned reactants or catalysts the process of the invention is preferably carried out at temperatures in the range from about 50 C. to about 150 C. More preferably, the interesterification reactions of this invention are carried out at temperatures in the range from about 75 C. to about 125 C.

Since the reaction of the present invention is an interesterification in which inositol is reacted with a fatty ester, the resulting product of the reaction will constitute an equilibrium mixture of inositol, esters thereof, displaced alcoholic substance from the ester originally employed, and esters of such alcoholic substance. Thus, if triglycerides are reacted with inositol, the product of the reaction will contain monoand diglycerides as well as inositol esters. If it is desired to obtain inositol esters which are not so contaminated with original esters and derivatives thereof, then it is preferable to react fatty esters of relatively volatile alcohols such as methyl or ethyl alcohol with the inositol. In this way, unreacted volatile esters can be readily separated from the reaction products by distillation or crystallation procedures, or the reaction can be carried out under reduced pressure so that the volatile alcohols formed as a result of the interesterification reaction are removed from the reaction zone substantially as rapidly as they are liberated. Such removal of volatile reaction products will substantially promote the conversion of the fatty ester of the volatile alcohol to inositol fatty ester.

Under any of the foregoing conditions it has been found that the interesterification reactions herein disclosed will be substantially complete within one hour. No aldverse effects have been noted if the reactants are allowed to remain in contact under interesterification conditions for considerable lengths of time, e.g. several hours, after the esterification is substantially complete From a practical standpoint, however, little advantage would accrue from such practice.

The inositol partial fatty esters to the preparation of which this application is directed can be utilized as emulsifiers in the preparation and formulation of edible products. For example, these esters are useful in the preparation of cakes, candy, chewing gum, licorice, peanut butter and various beverages. In addition, and inasmuch as inositol is presently utilized in pharmaceutical preparations, the partial esterification of the inositol in accordance with the present invention may result in better assimilation by the body of the inositol with a consequent en hanced pharmacological effect.

The following examples, in which amounts of all materials are expressed in parts by weight, will illustrate the manner in which the invention can be practiced. It is to be understood that the specific conditions set forth in the examples are not to be considered limiting of the invention which is defined only by the scope of the appended claims.

- Example I 7.21 parts of inositol was heated to 100 C. in 72 parts of dimethyl sulfoxide. After the inositol had dissolved 17.8 parts of a mixture of soybean oil and 20% cottonseed oil hydrogenated to an iodine value of about 7'6 and 2.5 parts of a 10% suspension of sodium methoxide in xylene was added. The resulting mixture was maintained at a temperature of about C. and agitated. After one hour the catalyst in the reaction mix was inactivated by the addition of about 10 parts of a 50% aqueous acetic acid solution.

The reaction mixture was then taken up in a 4:1 ethyl acetate and N-butanol mixture and washed three times with hot Water. The ethyl acetate-N-butanol solvent was removed from the washed mixture by evaporation on a steam bath under a nitrogen atmosphere. The mixture, substantially free of the solvent, was then steam deodorized at a pressure of 1 mm. of mercury for one-half hour at a temperature of to C.

The product was found, upon analysis, to have a hydroxyl value of 326.2 and a total fatty acid content of 79.09%. The formation of partial esters of inositol is indicated by the hydroxyl value which may be compared with the hydroxyl values of partially esterified inositol set forth in the table below.

The product of the preceding example can be elfectively used as an adjuvant in plastic shortenings wherein its emulsifying characteristics promote improved performance of the plastic shortening in the preparation of baked goods.

Example II 9 par-ts of inositol, 5.4 parts of methyl palmitate and about 200 parts of dimethylsulfoxide were introduced into a reaction vessel provided with mechanical stirring means. This mixture was heated to about 100 C. and then about 1% by weight of the methyl palmitate of a suspension of about 9% sodium methoxide catalyst in xylene was added to the heated mixture. The resulting mixture Was reacted for one hour at 100 C. and under a pressure of about 30 mm. of mercury. A reduced pressure was utilized so that a portion of the methanol formed as a by-product of the reaction could be removed from the reaction mixture. After one hour the catalyst was inactivated by the addition of a 50% aqueous solution of acetic acid.

The reaction product was then taken up in a 1:4 mixture of butanol and ethyl acetate solution and was waterwashed four times after which the butanol-ethyl acetate mixture was removed from the product by evaporation under vacuum. The resultant product was crystallized from about 20 parts of a 1:1 mixture of dioxane and ethyl ether at 10 C. and vacuum dried for 18 hours at 70-80" C.

The ester product was found by analysis to have a hydroxyl value of 604.2 and a total fatty acid content of 62.8%.

Equivalent amounts of methyl laurate, glycol monooleate, glycol distearate etc., can be substituted for methyl palmitate to give an inositol ester of substantially the same degree of completeness of esterification.

Example III The process of Example H was repeated except that 13.5 parts of methyl palmitate was reacted with 9 parts of inositol and that 100 parts of dimethyl sulfoxide solvent was used as the reaction medium.

The ester product of this process was found by analysis to have a hydroxyl value of 522.5 and a total fatty acid content of 68.4%.

In the foregoing examples the hydroxyl values (H.V.) and percent total fatty acids (T.F.A.) of the ester products were determined in accordance with Official Method CD4-40 and Tentative Method G3-53 respectively of the Official and Tentative Methods of the American Oil Chemists Society.

That the ester products produced in accordance with the process of this invention are the partial esters of inositol is evident from a comparison of the hydroxyl values of the products of the foregoing examples with the following calculated values for the partial palmitic acid It will be observed that the hydroxyl values of the products produced in accordance with the specific examples are not precisely in agreement with the calculated values set forth in the above table. Since the foregoing calculated values represent the values characteristic of the individual pure partial esters of inositol, and since, as has been pointed out hereinbefore, the reactions set forth in the examples are interesterification reactions, which will result in a product which is an equilibrium mixture of the original reactants and variou esters thereof, the calculated and analytically obtained values could not be expected to precisely agree. Rather, the analytically determined values, unless, of course a separation of the relatively pure individual ester had been made, would represent the presence in the ester product of a predominant amount of the particular individual ester, the calculated hydroxyl value of which is most closely approximated.

6 Having thus described the invention, what is claimed is:

1. A process for preparing partial fatty esters of inositol which comprises reacting inositol with a fatty acid ester selected from the group consisting of the fatty acid esters of aliphatic primary mono-hydroxy alcohols having from 1 to about 8 carbon atoms and fatty acid esters of polyhydric alcohols having not more than 3 carbon atoms in the presence of an interesterification catalyst at a temperature of from about C. to about 150 C. and in the presence of dimethylsulfoxide.

2. The process for preparing partial fatty esters of inositol which comprises reacting inositol with a fatty acid ester selected from the group consisting of the fatty acid esters of aliphatic primary mono-hydroxy alcohols having from 1 to about 8 carbon atoms and the fatty acid esters of polyhydric alcohols having not more than 3 carbon atoms, in the presence of an interesterification catalyst at a temperature in the range from about to 125 C. and in the presence of dimethylsulfoxide.

3. A process for preparing partial fatty esters of inositol which comprises reacting inositol with a fatty acid ester of glycerol in the presence of from about 0.1 to about 2.0% of an interesterification catalyst by weight of the glycerol ester, at a temperature in the range from about 75 to 125 C. in a reaction medium comprising essentially dimethylsulfoxide.

4. The process of claim 3 wherein the fatty acid ester of glycerol is a triglyceride.

5. The process for preparing partial fatty esters of inositol which comprises reacting inositol and a fatty triglyceride in the presence of an interesterification catalyst at a temperature of about C. in a reaction medium comprising essentially dimethyl sulfoxide, inactivating the catalyst by acidulation and thereafter freeing the reaction mixture of dimethylsulfoxide and unreacted inositol.

References Cited in the file of this patent UNITED STATES PATENTS 2,357,077 Brown Aug. 29, 1944 2,357,078 Brown Aug. 29, 1944 2,812,324 Huber et a1 Nov. 5, 1957 2,893,990 Hass et al. July 7, 1959 OTHER REFERENCES Rheineck et al.: The Journal of The American Oil Chemists Society, July 1954, vol. 31, pp. 306 to 311. 

1. A PROCESS FOR PREPARING PARTIAL FATTY ESTERS OF INOSITOL WHICH COMPRISES REACTING INOSITOL WITH A FATTY ACID ESTER SELECTED FROM THE GROUP CONSISTING OF THE FATTY ACID ESTERS OF ALIPHATIC PRIMARY MONO-HYDROXY ALCOHOLS HAVING FROM 1 TO ABOUT 8 CARBON ATOMS AND FATTY ACID ESTERS OF POLYHYDRIC ALCOHOLS HAVING NOT MORE THAN 3 CARBON ATOMS IN THE PRESENCE OF AN INTERESTERIFICATION CATALYST AT A TEMPERATURE OF FROM ABOUT 50*C. TO ABOUT 150*C. AND IN THE PRESENCE OF DIMETHYLSULFOXIDE. 